neopentyl diethoxyphosphorylmethanesulfonate | 189444-41-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: neopentyl diethoxyphosphorylmethanesulfonate
• 英文别名: Methanesulfonic acid, (diethoxyphosphinyl)-, 2,2-dimethylpropyl ester；2,2-dimethylpropyl diethoxyphosphorylmethanesulfonate
• CAS: 189444-41-5
• 化学式: C₁₀H₂₃O₆PS
• 分子量: 302.329
• InChiKey: JDIJFZDJYGQFJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  neopentyl diethoxyphosphorylmethanesulfonate 在 正丁基锂 、 三异丙基硅烷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid 2,2-dimethylpropyl ester trifluoroacetic acid salt
  参考文献：
  名称：

  Synthesis and separation of tritiated inhibitors of aminopeptidase A and their prodrugs

  摘要：

  为了研究两种相关的氨基肽酶 A (APA) 抑制剂的生物利用度，我们合成了三硫化二硫原药。这些分子是 4,4′-二硫代双-(3,3′-氨基)-1,1′-丁烷磺酸（RB 150）及其 2,2-二甲基丙酯（RB 151），每个单体在第 2 位有一个氚原子，纯度很高，最终的比活度约为 30 Ci/mmol。通过还原 RB 150 的二硫键，得到了对 APA 有 Ki=270 nM 的活性放射性标记抑制剂 EC 33。Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.888

文献信息

• Straightforward and Diastereoselective Synthesis of Tetrafunctionalized Thiol Synthons for the Design of Metallopeptidase Inhibitors
  作者：Christelle David、Laurent Bischoff、Bernard P Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1016/s0040-4020(99)00922-9

  日期：2000.1

  Tetrafunctionalized thiol-containing synthons with different side-chains have been prepared with good yields by a straightforward diastereoselective and general methodology. The key step of the synthesis consisted of a tandem reduction and Wittig–Horner reaction, which conserved the stereochemistry of the starting material. The method was generalized to different side-chains, allowing synthons for

  已经通过简单的非对映选择性和通用方法以良好的产率制备了具有不同侧链的四官能化的含硫醇的合成子。合成的关键步骤包括串联还原反应和Wittig-Horner反应，这保留了起始原料的立体化学。该方法被推广到不同的侧链，使合成用于设计各种锌金属肽酶抑制剂的合成子变得容易。
• Novel derivatives of 4,4' dithiobis-(3-aminobutane-1-1-sulfonates) and compositions comprising the same
  申请人：Roques Pierre Bernard

  公开号：US20060205695A1

  公开（公告）日：2006-09-14

  The invention relates to derivatives of 4,4′-dithiobis-(3-aminobutane-1-sulfonates) of formula (1), of use for the treatment and prevention of primary and secondary arterial hypertension.

  本发明涉及公式（1）的4,4'-二硫基双(3-氨基丁烷-1-磺酸酯)的衍生物，用于治疗和预防原发性和继发性动脉高血压。
• Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme
  作者：Christelle David、Laurent Bischoff、Hervé Meudal、Aurélie Mothé、Nadia De Mota、Sophie DaNascimento、Catherine Llorens-Cortes、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm9903040

  日期：1999.12.1

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.
• US7582797B2
  申请人：——

  公开号：US7582797B2

  公开（公告）日：2009-09-01
• Synthesis and separation of tritiated inhibitors of aminopeptidase A and their prodrugs
  作者：Nicolas Inguimbert、Pascale Coric、Hélène Dhotel、Catherine Llorens-Cortes、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1002/jlcr.888

  日期：2004.11

  With the aim of studying the bioavailability of two related aminopeptidase A (APA) inhibitors, we have synthesized tritiated disulfide prodrugs. These molecules, 4,4′-dithiobis-(3,3′-amino)-1,1′-butanesulfonic acid (RB 150) and its 2,2-dimethylpropyl ester(RB 151) bearing one tritium atom per monomer in position 2 were obtained with high purity and a final specific activity of about 30 Ci/mmol. The active radiolabeled inhibitor EC 33, Ki=270 nM for APA was obtained by reduction of the disulfide bond of RB 150. Copyright © 2004 John Wiley & Sons, Ltd.

  为了研究两种相关的氨基肽酶 A (APA) 抑制剂的生物利用度，我们合成了三硫化二硫原药。这些分子是 4,4′-二硫代双-(3,3′-氨基)-1,1′-丁烷磺酸（RB 150）及其 2,2-二甲基丙酯（RB 151），每个单体在第 2 位有一个氚原子，纯度很高，最终的比活度约为 30 Ci/mmol。通过还原 RB 150 的二硫键，得到了对 APA 有 Ki=270 nM 的活性放射性标记抑制剂 EC 33。Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.